{"id":"084ba186-f1ee-5f0c-9a64-5e67eeb94b40","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-p2x4-potentiation","predicate":"increases_activity_of","statement":"Ivermectin was a specific positive allosteric effector of heterologously expressed P2X4 channels with an EC50 near 250 nanomolar, increasing current amplitude and slowing deactivation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"c4bff057-9509-5e42-b990-7560cb89ee42","mechanism_event_label":"Ivermectin was a specific positive allosteric effector of heterologously expressed P2X4 channels with an EC50 near 250 nanomolar, increasing current amplitude and slowing deactivation.","subject":{"id":"416b9886-c6a5-5526-a8bf-b571a8d418bf","slug":"ivermectin","display_name":"Ivermectin","entity_type_key":"drug"},"object":{"id":"15b750d6-4e83-5abb-b460-620d238b688c","slug":"p2rx4","display_name":"P2X4 receptor channel / P2RX4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"c4bff057-9509-5e42-b990-7560cb89ee42","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-p2x4-potentiation-event","event_type":"observed_relationship","label":"Ivermectin was a specific positive allosteric effector of heterologously expressed P2X4 channels with an EC50 near 250 nanomolar, increasing current amplitude and slowing deactivation.","description":"Ivermectin was a specific positive allosteric effector of heterologously expressed P2X4 channels with an EC50 near 250 nanomolar, increasing current amplitude and slowing deactivation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"416b9886-c6a5-5526-a8bf-b571a8d418bf","slug":"ivermectin","display_name":"Ivermectin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"15b750d6-4e83-5abb-b460-620d238b688c","slug":"p2rx4","display_name":"P2X4 receptor channel / P2RX4","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Acute","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Heterologously expressed P2X4 and P2X4/P2X6 channels","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Submicromolar ivermectin, rapid and reversible","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The effect was specific to P2X4 and absent at P2X2, P2X3, P2X2/P2X3 and P2X7, so it cannot be generalised to ATP signalling as a whole.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Heterologously expressed P2X4 and P2X4/P2X6 channels","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Ivermectin was a specific positive allosteric effector of heterologously expressed P2X4 channels with an EC50 near 250 nanomolar, increasing current amplitude and slowing deactivation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Allosteric control of gating and kinetics at P2X(4) receptor channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10460235/ DOI: 10.1523/JNEUROSCI.19-17-07289.1999","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"ATP-gated cation channel gating and kinetics","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"cff2ff2e-ce49-5b58-8be9-30d8d8426337","evidence_kind":"source_excerpt","locator":"Lines 90-99","start_line":90,"end_line":99,"excerpt":"## ivermectin-p2x4-potentiation\nIvermectin was a specific positive allosteric effector of heterologously expressed P2X4 channels with an EC50 near 250 nanomolar, increasing current amplitude and slowing deactivation.\nModel/species: Heterologously expressed P2X4 and P2X4/P2X6 channels\nTissue/system: ATP-gated cation channel gating and kinetics\nExposure: Submicromolar ivermectin, rapid and reversible\nRoute: In vitro\nDuration: Acute\nLimits: The effect was specific to P2X4 and absent at P2X2, P2X3, P2X2/P2X3 and P2X7, so it cannot be generalised to ATP signalling as a whole.\nPrimary reference: Allosteric control of gating and kinetics at P2X(4) receptor channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10460235/ DOI: 10.1523/JNEUROSCI.19-17-07289.1999\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"20818ddd-7b37-5226-a24b-7de007e80eb2","stable_key":"import-e0801c92-7fd3-5cb2-82b7-dd82f010f3ed","title":"Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text.","file_path":"","sha256":"c7e1e0201cbd222f0c52b7981f078936ed39b617d747821ed6daa584c2b964a7","revision_id":"56746c3e-cdec-5b8f-a191-425de1a0a7ce","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}